As I have long been committed to a career as an academic biomedical researcher, a primary factor in my choice of pathology as a specialty was its substantial research opportunities. Despite my strong scientific background, the three and one half years I have spent in clinical service have left me in need of additional research training before attempting an academic career on my own. Having finished the clinical phase of my pathology residency, I am now devoting essentially all of my time to continuing my inquiries into the molecular basis of tumorigenesis. In both fetal brain in vivo, and retinoic acid-treated neuroblastoma in vitro, neuronal differentiation is accompanied by a significant decrease in the expression of the c-myb oncogene. This decline of c-myb RNA precedes both growth cessation and loss of phenotypic transformation, implying a potential biologic role for this gene product. Our preliminary observation of a neuroblastoma cell c-myb protein that is larger in size than its hematopoietic cell counterpart suggests a possible neuron-specific structural alteration. The experiments proposed here are designed to: 1) characterize the structure of this alternatively-sized neuronal myb protein, and 2) determine its function in the processes of neuronal cell growth, differentiation and tumorigenicity. Structural studies will involve cloning the c-myb cDNA from both normal fetal brain and human neuroblastomas as well as RNase protection, RNA-PCR, and immunoprecipitation. C-myb function will be assessed by measuring proliferation, differentiation, and transformation of neuroblastoma cells in which c-myb has either been artificially inhibited or induced. In addition, c-myb expression will be examined in neural tissue from developing rat embryos and from human-neural crest-derived tumors. These studies should allow a characterization of the amount, location,and timing of c-myb expression during the maturation and transformation of neuronal cells both in vitro and in vivo. Although these aims are ambitious, the structural studies in particular should be hastened by the substantial expertise of this lab in all areas of molecular biology. Innumerable technical and intellectual benefits should result from my association with this highly successful research team. The productive nature of the entire lab environment will serve as an excellent role model upon which to base my plans for an academic career as an independent biomedical scientist.